1. Field of the Invention
The present invention relates to an apparatus for white light observation and fluorescence diagnosis of skin diseases and, more particularly, to an apparatus for photodynamic diagnosis in which a plurality of excitation light emitting diodes (LEDs) is provided in an image pick-up head, the excitation LEDs being arranged to illuminate the entire examination region in the form of a mosaic by setting respective illumination light axes of the excitation LEDs to illuminate preassigned individual areas of the examination region, thus uniformly illuminating the examination region in a wide field of view with excitation light.
Moreover, the present invention relates to an apparatus for photodynamic diagnosis in which warm white LEDs and cold white LEDs as white light sources are appropriately arranged so as to deliver natural colors and thereby to reproduce natural color images.
2. Background Art
Recently, a variety of skin diagnosis apparatuses can be found in cosmetic shops, skin care clinics, and the like. With the skin diagnosis apparatus, a user can analyze and diagnose its skin condition so as to select cosmetics suitable for the skin condition or to find a problem in its skin condition and obtain a solution to the problem.
Among them, a skin diagnosis apparatus using a diagnostic lamp has been widely used for diagnosing the skin condition by irradiating a light beam of a predetermined wavelength onto the skin and analyzing a specific fluorescence emitted from the skin.
Conventional skin diagnosis apparatuses will be described with reference to literatures as follows.
Skin pores of a human body have sebaceous glands producing sebum, and the sebaceous glands in a healthy body secrete an appropriate amount of sebum from the skin pores to the skin surface to form a sebaceous membrane acting as a natural protecting layer.
However, an unhealthy body secretes an excessive amount of sebum and the sebum excessively secreted soon becomes oxidized by air, and the oxidized sebum becomes stickier and clogs the pores.
Bacteria propagate in the thus clogged pores and porphyrins are produced from the bacteria. The produced porphyrin emits light in response to ultraviolet light.
Accordingly, a skin diagnosis apparatus using porphyrin properties responsive to ultraviolet light has been developed.
The conventional skin diagnosis apparatus uses a method in which an ultraviolet lamp irradiates a patient's entire face in a dark box to observe a change in fluorescence intensities with naked eyes through a detector.
Moreover, optical fiber light sources based on the use of various kinds of lamp, such as halogen, xenon, metal-halide, mercury, etc., which are well known for the purpose of photodynamic diagnosis of diseases are developed and widely used.
Such lamps have been selected to meet the apparatus requirements in terms of specific medical purposes and means, technical and economical aspects. In a case where a complicated operation that should use a wide range of light intensities or a variety of light beams of selective wavelengths is required, the use of a single lamp could not provide an optimal method in general.
In this case, the developer of the apparatus has depended on a lamp having a specific function or used a plurality of lamps simultaneously to overcome the drawbacks. Especially, it has been known that it is necessary to observe geometry, position, color of an examination region by a white light in addition to the observation of fluorescence generated from the examination region by an excitation light irradiation in diagnosing diseases using fluorescence.
Advantages, possibilities and recent trends in use of fluorescence diagnosis (FD) and photodynamic therapy (PDT) of skin diseases using a photosensitizer including 5-aminolevulinic acid (5-ALA) have been described in the reference literature (C. Fritch and T. Ruzichka, “Fluorescence Diagnosis and Photodynamic Therapy of Skin Diseases”, Atlas and Handbook, 2003, Springer-Verlag. Wien).
According to the literature, a fluorescence image of a dermal layer is recorded in the form of a photograph in such a manner that the examination region is exposed to ultraviolet light of a Wood's lamp in a dark room for 0.25 to 1.5 seconds to take a photograph and the photograph is developed with a high sensitivity film such as 1600 ASA.
Meanwhile, U.S. Pat. No. 5,363,854 has disclosed a method for detecting anomalies of the skin, more particularly melanoma, and an apparatus for carrying out the method, in which an ordinary video camera fixed with a light source in a picture processing unit is used for detecting a fluorescence picture of an examination region and a reference picture.
The apparatus includes a light source for illuminating a two-dimensionally extending examination region of the skin, successively, with ultraviolet light range and with visible light.
The camera records a fluorescence picture of the examination region having signal values F(x,y) at its picture points x,y in response to the illumination with ultraviolet light and a reference picture having signal values R(x,y) at its picture points x,y in response to the illumination with visible light.
Moreover, a memory stores the signal values of at least one of the fluorescence picture and said reference picture, and a processor responsive to the memory produces an output picture having respective signal values A(x,y) at its picture points x,y which are formed from respective quotients F(x,y)/R(x,y) of the signal values of the fluorescence and reference pictures at the same picture points.
The image observed through an ocular of the apparatus is reorganized with two color images through a dichroic mirror, and the light source operates under continuous conditions or under impulse conditions and it saves energy and reduces the effect of extraneous light under the impulse conditions.
Moreover, the apparatus for detecting skin diseases includes an excitation light source for generating fluorescence from the examination region. The fluorescence generated along the reference light are divided by a beam splitter and sent to respective optical paths, the respective optical paths produce images in the examination region, and an optical coupler provides the images produced by the respective optical paths so that a user can observe the images with naked eyes.
U.S. Pat. No. 5,760,407 has proposed a device for the identification of acne, microcomedones, and bacteria on human skin.
Meanwhile, for the purpose of the diagnosis of skin diseases, there have been developed a series of photo-diagnostic methods using spectroscopy and imaging methods.
For the purpose of the skin therapy, there have been disclosed phototherapy methods by the action of electromagnetic radiation, and fluorescence diagnosis and photodynamic therapy (PDT) occupy an important place in such a series of photo-diagnostic methods.
In case of the fluorescence diagnosis, fluorescent characteristics observed in the diseased tissue region and in the normal tissue region are different from each other, and this difference is shown as emitted wavelength and fluorescence intensity.
One of the drawbacks in the spectroscopic wavelength calibration is that the spatial resolution in the examination region is low and the number of spots examined is small.
The method of obtaining the fluorescence image from the examination region eliminates the above drawback and the fluorescence images observed in most cases are given in the form of a monochrome fluorescence image.
Accordingly, for the purpose of an accurate morphological analysis, a color image acquired simultaneously by a white light from the same examination region is supplemented with the monochrome fluorescence image [simultaneous acquisition and display of morphological (color image) and physiological (fluorescence image) information) (DYADERM professional, Biocam GmbH; http://www.biocam.de].
However, as the monochrome fluorescence image loses information showing the difference of wavelengths in the individual skin regions, the quality of the image is substantially poor and it makes it difficult to investigate the cause of the fluorescence in study on the intrinsic fluorescence characteristics produced in the skin itself.
Meanwhile, it is possible to combine the advantages of the fluorescence spectroscopy method and the fluorescence imaging method by a multispectral imaging system [Hewett et al., 2000, “Fluorescence detection of superficial skin cancer,” J. Mod. Opt. 47, 2021-2027].
Moreover, the basic spectroscopic information of the fluorescence produced from the skin can be obtained from the visible light range and thereby it is possible to apply a high sensitive color camera to the multispectral imaging system, thus simplifying the configuration of the apparatus and improving the spatial resolution as well.
Meanwhile, according to an apparatus for the white light observation and fluorescence diagnosis of skin diseases, it is possible to observe the skin tissue using an image pick-up head, and the image pick-up head includes an image pick-up device for picking-up an image of the skin through a view hole being in contact with the skin, and an illumination system.
In general, light emitting diodes (LEDs) having an illumination range of 395 nm to 405 nm have been used as fluorescence excitation light sources in the illumination system of the image pick-up head, and white LEDs have been used as white light sources.
Moreover, the field of view of the examination region, i.e., the region to be examined through the view hole, is generally about 20 mm. The light observation may be made through a television camera, for example, a color CCD-415: ½ inch, 782×582), and the image recording and image processing of the fluorescence and white light are simultaneously available.
As an excitation light source for exciting the fluorescence emitted from the diseased region, a diode that emits light in the ultraviolet range has been used. However, the light irradiation in the ultraviolet wavelength range has the following problems.
(1) As the excitation light is irradiated in the excitation wavelength range of collagen (320 nm to 380 nm), it is difficult to observe the fluorescence produced from other fluorescence sources of the skin due to a blue fluorescence in the vicinity of 400 nm produced from collagen extensively distributed in the skin.
(2) Since the main absorption band of porphyrins in Propionibacterium acnes is in the vicinity of a wavelength of 400 nm, the light efficiency for exciting the fluorescence is decreased.
(3) The ultraviolet rays used are harmful to the human body and hard to penetrate subcutaneous tissue.
Besides, if the ultraviolet LED lights are arranged circularly around the image pick-up light axis and the illumination light axes are collected to the center of the view hole, the illuminated regions by the LED lights should overlap each other based on the image pick-up light axis in order to obtain a UV illumination light of a uniform intensity in the view hole, and thereby the illuminated regions by the LED lights are limited to a very narrow range.
That is, if the LEDs are used as light sources, it has a basic problem of non-uniformity due to the characteristic that the illumination intensity is large in the center of the LEDs but becomes smaller as it comes nearer to the periphery.
Of course, in a case where a plurality of LEDs is arranged circularly in the image pick-up head, if the LEDs (excitation LEDs) 10 are arranged at the same illumination angle so that the illuminated regions overlap each other based on the light axis as shown in FIG. 6, the non-uniformity problem is somewhat solved. However, while the fluorescence image quality is satisfactory in the center of the field of view on the examination region, the image quality is still not good in the peripheral region due to insufficient illumination intensity. Especially, it is necessary to ensure a sufficient distance between the LEDs and the examination region, and thereby the illuminated regions by the LED lights are limited to a very narrow range.
If the sensitivity of the camera is increased to sufficiently illuminate the periphery, the central portion comes into a saturated condition.
Hereinafter, the non-uniformity problem of illumination in accordance with the conventional skin diagnosis apparatus will be described in more detail.
In order for the light emitting diode itself to provide a high uniformity of illumination, it is necessary to decrease the difference in intensities between the center of a spot illuminated by the LED and the boundary thereof, if possible.
Using RL-UV2030 (405 nm), one of the LEDs having excellent characteristics, as a sample LED, and varying the distance between the emission peak of the LED and the object region, the output densities in the spot center of the illumination beam according to the distances, and the diameters of the spots showing an intensity of 50% of the maximum intensity of the spot center were measured (using a detector with a diameter of 8 mm in an optical power meter Q8230), and the measurement results are shown in the following table 1:
TABLE 1Distance between emission peak ofLED and object region (mm)2025303540455055Output density (with filter)5.74.63.42.62.01.51.31.1(mW/cm2)(4.27)(3.45)(2.55)(1.95)(1.5)(1.12)(0.97)(0.82)Diameter at 50% intensity8.810.512.314.115.917.619.421.4
As can be seen from table 1, if a single LED is used to obtain an illumination required to observe the field of view, it is difficult to obtain a desired illumination.
That is, if the object region is illuminated from a close distance, the diameter of the illumination beam is insufficient, whereas, if illuminated from a far distance, the output density of the illumination beam is insufficient.
Accordingly, it is necessary to increase the number of LEDs so as to increase the output density of the illumination, and it may consider a variety of arrangements of the LEDs for a uniform illumination.
The simplest method is to employ, for example, twelve LEDs 10 in front of a camera 1 and to orient illumination light axes C2 of the LEDs 10 toward the center of the field of view as shown in FIG. 6. In this case, it is possible to obtain a uniform illumination as the diameter of the field of view is 21.4, in which the output density calculated in the center of the field of view is 9.9 mW/cm2.
However, such an arrangement requires a considerable amount of free space from a fixing plate of the LEDs to the examination region, i.e., the view hole region, in the case of the image pick-up head, and from the LEDs to the examination region. Accordingly, it is necessary to ensure a sufficient distance from the LEDs to the examination region.
For example, such a distance should be more than 60 mm.
As a result, since the distance from the LEDs 10 to the view hole to be in contact with the examination region becomes long, it is inevitable that the entire length of the image pick-up head becomes long in order to ensure a sufficient distance.
Another method is to arrange the LEDs more adjacent to the view hole of the case in order to reduce the amount of free space by increasing the number of LEDs. The arrangement and illumination state of the LEDs used as excitation light sources in this case are shown in FIGS. 7 and 8.
In this case, twenty LEDs 10 are used as fluorescence excitation light sources, in which twelve LEDs are arranged around a circle with a diameter of 20 mm at regular intervals as shown in FIG. 7. Moreover, as shown in FIG. 8, the LEDs are arranged to have an angle α of 16° of an illumination light axis C2 based on an image pick-up light axis C1, i.e., a central axis of a camera 1, and arranged to have a distance of about 30 mm from the examination region, i.e., the view hole region.
The other eight LEDs are arranged around a circle with a diameter of 28 mm as shown in FIG. 7, in which each four LEDs is arranged in the left and light sides of the figure and inclined at the same angle as the twelve LEDs to have the same angle a of the illumination light axis C2. Moreover, the eight LEDs are positioned adjacent to the examination region, for example, about 8 mm closer than the twelve LEDs.
The additional eight LEDs arranged more adjacent to the examination region as described above are auxiliary illuminations for illuminating the left and right edge regions based on the pick-up light axis.
In such an arrangement, the rated current required for the respective LEDs is 20 mA, and 30 mA in maximum. The illumination output density in the center of the field of view that, i.e., in the center of the examination region, is 8.5 mW/cm2 under the rated conditions (20 mA), and 12 mW/cm2 under the forced condition (30 mA).
The images obtained from an examination region by such an illumination system are shown in A of FIG. 9. As shown in the figure, while the quality of the fluorescence image in the center of the field of view is relatively good, the quality of the peripheral image is not good due to insufficient illumination intensity.
FIG. 9 shows fluorescence images obtained from the illumination system in which the LEDs arranged circularly to illuminate at the same angle, in which ‘A’ is a fluorescence image taken from the examination region (gain 8, N=0, gamma=20, R=G=B=0) at 160 mA, and ‘B’ is a fluorescence image obtained by increasing the light sensitivity of a detector (camera) under the same conditions as ‘A’.
Moreover, ‘C’ in FIG. 9 shows a fluorescence image of a standard model, in which contours are drawn at intensity intervals such as 30, 40, 50 and —70% of the maximum intensity. The diameters of the contours correspond to 72, 63, 54 and 40% of the diagonal size of the field of view (20.8 mm).
Furthermore, ‘D’ in FIG. 9 is a three-dimensional graphic showing an intensity distribution under the conditions of ‘C’. If the camera sensitivity is increased to examine the periphery in more detail, the central portion comes into a saturated condition like the image of ‘B’, and such a non-uniformity of illumination is called the hot-spot. The hot-spot can be readily observed by the three-dimensional graphic for the illumination intensity (see ‘D’ of FIG. 9).
Meanwhile, if the illumination light of the LED is to have a Lambertian distribution, it is possible to provide a uniform illumination. However, since the Lambertian illumination distributes the light on a wide range, the output density of the light obtained from a specific examination region is relatively low and it is impossible to obtain a desired image.
In order to increase the output density of the illumination light for a desired image, a large number of LEDs are required, which results in an increase in size of the diagnosis apparatus.
Moreover, the output of the illumination light scattered by the LEDs in the Lambertian illumination heats the case and the other components of the apparatus, which may cause a burn injury or discomfort to a patient.